CD73 and CD39 ectonucleotidases in T cell differentiation: Beyond immunosuppression

María Rosa Bono, Dominique Fernández, Felipe Flores-Santibáñez, Mario Rosemblatt, Daniela Sauma

Research output: Contribution to journalReview articlepeer-review

89 Citations (Scopus)


Extracellular ATP is a danger signal released by dying and damaged cells, and it functions as an immunostimulatory signal that promotes inflammation. However, extracellular adenosine acts as an immunoregulatory signal that modulates the function of several cellular components of the adaptive and innate immune response. Consequently, the balance between ATP and adenosine concentration is crucial in immune homeostasis. CD39 and CD73 are two ectonucleotidases that cooperate in the generation of extracellular adenosine through ATP hydrolysis, thus tilting the balance towards immunosuppressive microenvironments. Extracellular adenosine can prevent activation, proliferation, cytokine production and cytotoxicity in T cells through the stimulation of the A2A receptor; however, recent evidence has shown that adenosine may also affect other processes in T-cell biology. In this review, we discuss evidence that supports a role of CD73 and CD39 ectonucleotidases in controlling naive T-cell homeostasis and memory cell survival through adenosine production. Finally, we propose a novel hypothesis of a possible role of these ectonucleotidases and autocrine adenosine signaling in controlling T-cell differentiation.

Original languageEnglish
Pages (from-to)3454-3460
Number of pages7
JournalFEBS Letters
Issue number22
Publication statusPublished - 1 Jul 2015


  • Adenosine
  • CD39
  • CD73
  • Differentiation
  • Ectonucleotidase
  • T cell

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology


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